Bioreactor systems are used to produce biochemically active substances derived from organisms. Bioreactors are commonly tank systems including pumps, agitation systems, air distribution systems and sensors. Traditionally, bioreactors were designed as stationary reusable tanks or containers. More recently, disposable bioreactors, which may utilize plastic sterile bags, are becoming increasingly common. Disposable, single-use manufacturing systems can be assembled from component pieces (e.g. tubing, filters, bags, fittings, connectors, sensors, etc) into disposable assemblies. Component pieces and portable assembly capabilities provide advantages such as flexibility to rapidly change the configuration of the assembly. Bioreactor systems commonly include additional hardware to perform the upstream and downstream processing.
Exemplary downstream processing includes: harvest/clarification, chromatography, and ultrafiltration/diafiltration (UF/DF). When a bioreactor is ready to be harvested, the contents are often clarified. In one example, a peristaltic pump is used to transfer the contents of the bioreactor through a depth filter system and a disposable capsule filter to remove large molecules with high molecular weight from cells, cell debris, colloids and particles. Chromatography is a physical method of separation in which the components to be separated are distributed between two phases, one of which is stationary while the other (mobile) moves in a defined direction. Chromatography involves a product to be separated (purified) over a stationary support (resin). The molecules in the product will have different interactions (capture, purification, and polishing) with the stationary support leading to separation of similar molecules. Examples of liquid chromatography are Affinity, Hydrophobic Interaction “HIC”, and Ion-Exchange. UF/DF (Tangential Flow Filtration) steps are used to clarify, reduce batch volumes (concentration) and exchange buffers (diafiltration) for efficient column operation or final formulation. In Tangential Flow Filtration (TFF), the fluid is pumped tangentially along the surface of the membrane. An applied pressure (transmembrane pressure) serves to force a portion of the fluid through the membrane to the filtrate side. Particulates and macromolecules that are too large to pass through the membrane pores are retained but do not build up at the surface of the membrane. Instead, they are swept along by the tangential flow.
Exemplary upstream processing includes the processing associated with buffer and media preparation. Preparation of the bioreactor usually begins with the preparation of the inoculum which proceeds in scale-up steps until enough inoculum is made to aseptically inoculate the final, sterile, media-filled bioreactor.
Manufacturing Execution System (MES) software is used to provide real-time access to plant activities that include equipment, labor, orders and inventory. A MES integrates the data with enterprise resource planning (ERP) systems to enable control over the factory floor and supply chain.
Batching software systems are typically one component of the MES that are used to specify batching processes for bioreactor systems, including the upstream and downstream processing. The batching software systems are also used to create and manage recipes and execute them automatically on the bioreactor systems. The batching software also facilitates validation of recipes and configuration of the physical equipment. During the execution of the recipes, the batching software systems further usually collect detailed electronic batch data about the processes and generate detailed reports. Examples of batching software include InBatch by WONDERWARE®, PI System by OSISOFT®, PROFICY® Batch Execution by General Electric Company, SIMATIC PCS 7® process control system by Siemens, and FACTORY TALK® by Rockwell Automation, Inc.